title: Arginine vasopressin release inhibitor RU51599 attenuates brain oedema following transient forebrain ischaemia in rats.
abstract: RU51599 is an arginine vasopressin (AVP) release inhibitor and a selective kappa opioid agonist which has a pure water diuresis effect without associated electrolyte excretion. The effect of RU51599 on brain oedema following transient forebrain ischaemia in rats was examined. Under microscopy, the visible vertebral arteries at the second vertebra could be easily electrocauterized and completely cut by microscissors to yield complete cessation of circulation of both vertebral arteries. Transient forebrain ischaemia was induced by this improved highly reproducible technique of four-vessel occlusion model. Forty-three male Wistar rats were separated into six groups; saline-treated (1 ml/kg) normal rats (n = 10), RU51599-treated (1 mg/kg) normal rats (n = 4), saline-treated (1 ml/kg) rats with complete occlusion of both vertebral arteries (n = 5), RU51599-treated (1 mg/kg) rats with complete occlusion of both vertebral arteries (n = 5), saline-treated (1 ml/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n = 11), RU51599-treated (1 mg/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n = 8). The brain water content was determined by the dry-wet weight method. Cerebral blood flow was monitored during ischaemia and reperfusion was performed by laser Doppler flowmetry to make sure to obtain reversible forebrain ischaemia. Effects of RU51599 on concentration of glutamate released from the hippocampal CA1 of rats subjected to 5 minutes four-vessel occlusion and 60 minutes of reperfusion were also investigated by the microdialysis method. This modified four-vessel occlusion method produced reversible forebrain ischaemia with a high level of success. Bilateral carotid occlusion followed by 60 minutes reperfusion caused a significant increase in brain water content (P < 0.01), which was significantly attenuated by RU51599 (P < 0.01). These findings indicate that the AVP-release inhibitor RU51599 reduced brain oedema following transient forebrain ischaemia in rats.
authors.affiliation: Department of Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Toda
authors.forename: T
authors.initials: T
authors.lastname: Kawamoto
authors.forename: A
authors.initials: A
authors.lastname: Teramoto
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D044482:Benzeneacetamides; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications*; D002540:Cerebral Cortex / Q000098:blood supply; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis; D016548:Prosencephalon / Q000098:blood supply*; D011759:Pyrrolidines; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000627:therapeutic use
chemical_list: D044482:Benzeneacetamides; D004232:Diuretics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D001127:Arginine Vasopressin; C100946:niravoline